Jeanie Tsamis

My project is focused on understanding the role histones play in the mechanism of local gene repression. The Sum1 complex is an example of a locus specific repressor, acting at specific promoters in the genome. The complex contains Sum1p, a DNA binding protein, Hst1p, a NAD+ dependent histone deacetylase, and Rfm1p, which tethers the complex together. Histone H3 and H4 tails bind to Sum1p in vitro, suggesting that histones may play a direct role in the mechanism of repression through interactions with Sum1p. Hst1p deacetylase activity, specific to lysine residues within these tail regions, also assists in repression of Sum1p-regulated genes. Other regulatory systems in yeast, including the Sir silencing complex and Tup1-Ssn6 co-repressor complex, also demonstrate interaction with histone tails in vitro and require histone deacetylase activity for function, further supporting a role for histones in gene repression. To better understand the mechanism of local repression, I am identifying and characterizing the interaction domain between Sum1p and histones, and determining how the disruption of this interaction affects the mechanism of Sum1p-mediated repression in vivo.